No pharmacologic agent is known to accelerate and improve the quality of human wound healing in vivo. In preliminary work recombinant EGF accelerated the quality of experimental and human wound healing. Now that milligram quantities of EGF are available it is possible to determine mechanisms whereby EGF and related growth factors affect wound healing in vivo. This application will study processes mediating growth and proliferation of mammalian skin as they relate to wound healing in an in vivo porcine model and where possible in human patients. The specific aims are: 1) To extend histochemical, EM and morphometric studies using EGF and its receptor to define involvement of this factor in porcine and human wound healing; 2) To determine the sequential appearance and identity of cells activated during wound healing by EGF and other growth factors using binding, phosphorylation, and in situ autoradiography; 3) To determine by in situ hybridization if EGF-R during wound healing is modulated by receptor occupancy, ligand (EGF, TGF-A) or interactions with other factors (TGF-B); 4) To study the effects of EGF and related factors on epithelial and mesenchymal interactions by studying the sequential appearance, distribution and nature of extracellular matrix components namely collagens and fibronectin.